NM_000238.4(KCNH2):c.1894C>T (p.Pro632Ser) AND Cardiovascular phenotype

Clinical significance:Likely pathogenic (Last evaluated: Sep 17, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000621397.1

Allele description [Variation Report for NM_000238.4(KCNH2):c.1894C>T (p.Pro632Ser)]

NM_000238.4(KCNH2):c.1894C>T (p.Pro632Ser)

Gene:
KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q36.1
Genomic location:
Preferred name:
NM_000238.4(KCNH2):c.1894C>T (p.Pro632Ser)
Other names:
p.P632S:CCC>TCC
HGVS:
  • NC_000007.14:g.150951499G>A
  • NG_008916.1:g.31428C>T
  • NM_000238.3:c.1894C>T
  • NM_000238.4:c.1894C>TMANE SELECT
  • NM_001204798.2:c.874C>T
  • NM_172056.2:c.1894C>T
  • NM_172057.3:c.874C>T
  • NP_000229.1:p.Pro632Ser
  • NP_000229.1:p.Pro632Ser
  • NP_001191727.1:p.Pro292Ser
  • NP_742053.1:p.Pro632Ser
  • NP_742054.1:p.Pro292Ser
  • LRG_288t1:c.1894C>T
  • LRG_288t2:c.1894C>T
  • LRG_288:g.31428C>T
  • LRG_288p1:p.Pro632Ser
  • LRG_288p2:p.Pro632Ser
  • NC_000007.13:g.150648587G>A
  • NM_000238.2:c.1894C>T
  • Q12809:p.Pro632Ser
Protein change:
P292S
Links:
UniProtKB: Q12809#VAR_014378; dbSNP: rs199473527
NCBI 1000 Genomes Browser:
rs199473527
Molecular consequence:
  • NM_000238.3:c.1894C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000238.4:c.1894C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.2:c.1894C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.874C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000737460Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Sep 17, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT.

Circulation. 2000 Sep 5;102(10):1178-85.

PubMed [citation]
PMID:
10973849

Clinical characteristics of 30 Czech families with long QT syndrome and KCNQ1 and KCNH2 gene mutations: importance of exercise testing.

Andrsova I, Novotny T, Kadlecova J, Bittnerova A, Vit P, Florianova A, Sisakova M, Gaillyova R, Manouskova L, Spinar J.

J Electrocardiol. 2012 Nov-Dec;45(6):746-51. doi: 10.1016/j.jelectrocard.2012.05.004. Epub 2012 Jun 22.

PubMed [citation]
PMID:
22727609
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000737460.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The p.P632S variant (also known as c.1894C>T), located in coding exon 7 of the KCNH2 gene, results from a C to T substitution at nucleotide position 1894. The proline at codon 632 is replaced by serine, an amino acid with similar properties. This variant was reported in two studies of individuals and families reported to have long QT syndrome (LQTS)(SplawskiI et al.Circulation. 2000;102(10):1178-85;AndrsovaIet al.JElectrocardiol.2012;45(6):746-51). Onestudy with in vitro analysessuggestedthis alteration to result in abnormal protein trafficking (Anderson CL et al.NatCommun.2014;5:5535). In addition, another alteration affecting the same amino acid (p.P632A (c.1894C>G)) has alsobeen reported in association with LQTS (MullallyJ et al.Heart Rhythm. 2013;10(3):378-82).This variant was previously reported in the SNPDatabase as rs199473527. This variant was not reported in population-based cohorts in the following databases: NHLBIExome Sequencing Project (ESP), and 1000 Genomes Project.This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 25, 2021

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